CN105838592A - DNA sequencing device and manufacturing method - Google Patents
DNA sequencing device and manufacturing method Download PDFInfo
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- CN105838592A CN105838592A CN201610320198.0A CN201610320198A CN105838592A CN 105838592 A CN105838592 A CN 105838592A CN 201610320198 A CN201610320198 A CN 201610320198A CN 105838592 A CN105838592 A CN 105838592A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
Abstract
The invention provides a DNA sequencing device and a manufacturing method. The device mainly comprises a silicon dioxide thin film arranged on a double-side polished monocrystalline silicon piece. A silicon nitride thin film grows on the top of the silicon dioxide thin film. A bottom layer contact electrode is prepared on the silicon nitride thin film and covered with a bottom layer graphene micro-strip. The bottom layer graphene micro-strip is covered with a hexagonal boron nitride micro-strip. The hexagonal boron nitride micro-strip is covered with a top layer graphene micro-strip. A graphene-hexagonal boron nitride-graphene heterostructure is formed by the bottom layer graphene micro-strip, the hexagonal boron nitride micro-strip and the top layer graphene micro-strip. Graphene-hexagonal boron nitride-graphene nano-pores are etched. According to the device, the problem that a conventional solid-state nano-pore channel is too long, so that the sequencing resolution ratio does not reach single base is solved, and the problem that a tunneling electrode is difficult to manufacture in a tunneling current DNA sequencing method is solved. The advantages lay a foundation for achieving single base resolution ratio and direct nano-pore sequencing.
Description
Technical field
The present invention relates to DNA sequencing technical field, particularly relate to a kind of DNA sequencing device and preparation method.
Background technology
DNA (DNA) sequencing technologies is one of core technology of modern life science research.From
First generation sequencing technologies of based on fluorescence labeling Sanger method is to circular array synthesis PCR sequencing PCR as representative
Second generation sequencing technologies, greatly changes people and studies the mode of all life blueprints, promoted gene
Organize and the foundation of related discipline and development.
But, through the development of many decades, first generation sequencing technologies is owing to depending on electrophoretic separation technique
Rely, speed with become present aspect to be reached the limit.Second generation sequencing technologies is due to fluorescence or change
Learn the dependence of luminescent substance so that instrument and equipment, the cost of biochemical reagents are difficult to significantly reduce.For realizing
Hundred dollars of human genome (HDG) targets, novel do not use the direct of any mark in the urgent need to a kind of
Sequence measurement.In all DNA sequencing technology of new generation with low cost, high flux, direct Sequencing as target
In, single-molecule sequencing based on nano-pore is considered as most promising DNA sequencing technology.
Up to now, DNA unimolecule direct Sequencing method based on nano-pore is broadly divided into two big classes: longitudinally
Gas current Blocking Method and horizontal tunnelling current method.The challenge of gas current Blocking Method is nanopore-channel mistake
Length causes order-checking precision to have much room for improvement.Laterally tunnelling current method needs to manufacture a pair at nano-pore edge apart
Being only the tunnelling electrode of about 1.5nm, order-checking precision is high but technology difficulty is big.Due to above-mentioned two class methods pair
The structural requirement of nano-pore is different, thus the most individually uses, and limits the essence of nanopore DNA order-checking
Degree and reliability.
Summary of the invention
The embodiment provides a kind of DNA sequencing device and preparation method, to realize DNA molecular
Accurately, efficiently, low cost order-checking.
To achieve these goals, this invention takes following technical scheme.
According to an aspect of the invention, it is provided a kind of DNA sequencing device, including:
The lower layer contacts electrode being arranged on twin polishing monocrystalline silicon piece, covers above lower layer contacts electrode
There is bottom Graphene micro-strip, above bottom Graphene micro-strip, be coated with hexagonal boron nitride micro-strip, six sides
Top layer graphene micro-strip, bottom Graphene micro-strip, hexagonal boron nitride micro-strip it is coated with above boron nitride micro-strip
A Graphene hexagonal boron nitride Graphene heterojunction structure is constituted, at stone with top layer graphene micro-strip
Ink alkene hexagonal boron nitride Graphene hetero-junctions center etching Graphene hexagonal boron nitride Graphene is received
Metre hole.
Further, including the silica membrane being placed on twin polishing monocrystalline silicon piece, this silica
Film grown on top has silicon nitride film, is etched with rectangular window on silicon nitride film, thin at silicon nitride
Photoetching and thermal evaporation or electron beam evaporation technique is utilized to prepare chrome gold lower layer contacts electrode on film.
Further, photoetching and plasma etching technology patterned graphene hexagonal boron nitride are utilized
Graphene heterojunction structure, utilizes photoetching and thermal evaporation or electron beam evaporation technique in top layer graphene micro-strip
Two top layer contact electrodes of side's preparation, utilize and focus on electron beam or focused ion beam technology at the graphite suspended
The Graphene hexagonal boron nitride of alkene hexagonal boron nitride Graphene hetero-junctions center one sub-10nm of etching
Grapheme nano-pore.
Further, the back side at monocrystalline silicon piece utilize dual surface lithography, inductively coupled plasma or respectively to
Opposite sex wet etching technique makes microcavity, is filled with electrolyte solution in sequencing reaction chamber, and reaction chamber is used for
Support silicon nitride film and the Graphene hexagonal boron nitride Graphene hetero-junctions on upper strata.
Lower layer contacts electrode connects positive potential, be positioned at Graphene hexagonal boron nitride grapheme nano-pore left,
The top layer contact electrode of right both sides connects positive potential and negative potential respectively.
Further, lower layer contacts electrode, top layer right contact electrode, longitudinally faint tunnelling current are measured
Equipment and variable voltage source constitute longitudinal tunnelling current and measure loop；
It is distributed in a pair top layer contact electricity of Graphene hexagonal boron nitride grapheme nano-pore the right and left
Equipment is measured in pole, horizontal faint tunnelling current and variable voltage source constitutes horizontal tunnelling current and measures loop；
It is placed in the platinum electrode above monocrystalline silicon piece and connects positive potential, be placed in the platinum electrode below monocrystalline silicon piece and connect negative
Current potential, platinum electrode, faint ion-conductance flow measurement device and variable voltage source constitute faint gas current and measure
Loop.
Further, a diameter of 1 10nm of described Graphene hexagonal boron nitride grapheme nano-pore.
Further, described top layer graphene micro-strip is single or multiple lift Graphene, described bottom Graphene
Micro-strip is single or multiple lift Graphene, and described hexagonal boron nitride micro-strip is single or multiple lift hexagonal boron nitride.
Further, it is used for driving single strand dna to pass Graphene hexagonal boron nitride graphene nano
The electrostatic field in hole is provided by variable voltage source, and the bias voltage of described variable voltage source should be 0.05
0.25V, the platinum electrode above Graphene hexagonal boron nitride grapheme nano-pore connects positive potential, at stone
Platinum electrode below ink alkene hexagonal boron nitride grapheme nano-pore connects negative potential.
Further, the right side in Graphene hexagonal boron nitride grapheme nano-pore top layer graphene
Contact one on negative potential, the lower layer contacts electrode on bottom Graphene connects positive potential, at Graphene
A pair top layer contact electrode of hexagonal boron nitride grapheme nano-pore the right and left connects positive potential respectively and bears
Current potential.
According to another aspect of the present invention, it is provided that the preparation method of a kind of DNA sequencing device, including such as
Lower step:
Step 1: wash down twin polishing monocrystalline silicon piece, monocrystalline silicon piece is placed in hydrogen peroxide that proportioning is 1:4 and
In sulfuric acid mixture liquid, described sulfuric acid mixture liquid is heated, remove the superficial stain of monocrystalline silicon piece, so
Afterwards with deionized water rinsing, dry monocrystalline silicon piece；
Step 2: by hot oxide growth layer of silicon dioxide film on monocrystalline silicon piece；
Step 3: utilize plasma enhanced chemical vapor deposition technology at silica membrane grown above
Layer silicon nitride film；
Step 4: utilize photoetching and thermal evaporation or electron beam evaporation technique to prepare Graphene hexagonal boron nitride
Chrome gold lower layer contacts electrode bottom Graphene hetero-junctions；
Step 5: utilize dual surface lithography technology and inductively coupled plasma or anisotropic wet etch technology
Microcavity is gone out at monocrystalline silicon piece back-etching；
Step 6: utilize photoetching technique and reactive ion etching technology to make a rectangle on silicon nitride film
Window, this rectangular window is for the Graphene hexagonal boron nitride Graphene heterojunction structure of support suspension；
Step 7: utilize polymethyl methacrylate transfer bottom Graphene micro-strip to lower layer contacts electrode and nitrogen
On SiClx film, as the tunnelling bottom electrode of Graphene hexagonal boron nitride Graphene hetero-junctions；
Step 8: utilize polymethyl methacrylate transfer hexagonal boron nitride micro-strip to bottom Graphene micro-strip
On, as the dielectric layer of Graphene hexagonal boron nitride Graphene hetero-junctions；
Step 9: utilize polymethyl methacrylate transfer top layer graphene micro-strip to hexagonal boron nitride micro-strip
On, as electrode in the tunnelling of Graphene hexagonal boron nitride Graphene hetero-junctions, and utilize photoetching and
Plasma etching technology patterned graphene hexagonal boron nitride Graphene heterojunction structure；
Step 10: utilize photoetching and thermal evaporation or electron beam evaporation technique to prepare in top layer graphene micro-strip
Two chrome gold top layer contact electrodes；
Step 11: utilize and focus on electron beam or focused ion beam technology in the Graphene six side nitridation suspended
The Graphene hexagonal boron nitride graphene nano of boron Graphene hetero-junctions center one sub-10nm of etching
Hole, this Graphene hexagonal boron nitride grapheme nano-pore contacts the centre of electrode at two top layers；
Step 12: will be installed on the sequence testing chip of Graphene hexagonal boron nitride grapheme nano-pore
In sequencing reaction chamber；Lower layer contacts electrode and right side top layer contact access between electrode variable voltage source and
Longitudinally faint tunnelling current measures equipment；It is being positioned at Graphene hexagonal boron nitride grapheme nano-pore
Access variable voltage source between the top layer contact electrode of arranged on left and right sides and horizontal faint tunnelling current measurement sets
Standby；Access between two platinum electrodes and drive single strand dna to pass through Graphene hexagonal boron nitride graphite
The variable voltage source of alkene nano-pore and faint ion-conductance flow measurement device.
The technical scheme provided by embodiments of the invention described above is it can be seen that present invention employs DNA molecular
When passing through Graphene hexagonal boron nitride grapheme nano-pore, in nano-pore longitudinal gas current block,
The change of horizontal tunnelling current, nano-pore top layer and bottom Graphene micro-strip in nano-pore top layer graphene micro-strip
Between longitudinal tunnelling current change the new thought of three groups of Data Analysis order-checkings.This three groups of Data Analysis are used to survey
More letters when sequence can provide single strand dna to pass through Graphene hexagonal boron nitride grapheme nano-pore
Breath, improves Conventional nano ionic porogen current blockade method signal to noise ratio low, easily by problems such as external interference.
Aspect and advantage that the present invention adds will part be given in the following description, and these are by from following
Description becomes obvious, or recognized by the practice of the present invention.
Accompanying drawing explanation
In order to be illustrated more clearly that the technical scheme of the embodiment of the present invention, institute in embodiment being described below
The accompanying drawing used is needed to be briefly described, it should be apparent that, the accompanying drawing in describing below is only this
Some bright embodiments, for those of ordinary skill in the art, are not paying creative work
Under premise, it is also possible to obtain other accompanying drawing according to these accompanying drawings.
The one that Fig. 1 provides for the embodiment of the present invention is based on Graphene hexagonal boron nitride grapheme nano-pore
The structural representation of DNA sequencing device；
The process chart of the preparation method of a kind of DNA sequencing device that Fig. 2 provides for the embodiment of the present invention.
Detailed description of the invention
Embodiments of the present invention are described below in detail, and the example of described embodiment is shown in the drawings,
The most same or similar label represents same or similar element or has same or like merit
The element of energy.The embodiment described below with reference to accompanying drawing is exemplary, is only used for explaining this
Bright, and be not construed as limiting the claims.
Those skilled in the art of the present technique are appreciated that unless expressly stated, singulative used herein
" one ", " one ", " described " and " being somebody's turn to do " may also comprise plural form.Will be further understood that
, the wording used in the specification of the present invention " includes " referring to there is described feature, integer, step
Suddenly, operation, element and/or assembly, but it is not excluded that existence or add other features one or more,
Integer, step, operation, element, assembly and/or their group.It should be understood that when we claim element quilt
" connecting " or during " coupled " to another element, it can be directly connected or coupled to other elements, or
Intermediary element can also be there is in person.Additionally, " connection " used herein or " coupling " can include nothing
Line connects or couples.Wording "and/or" used herein includes that what one or more was associated lists item
Any cell and all combinations.
Those skilled in the art of the present technique are appreciated that unless otherwise defined, all terms used herein
(including technical term and scientific terminology) has and one of the those of ordinary skill in art of the present invention
As understand identical meaning.Should also be understood that those terms defined in such as general dictionary should
It is understood to that there is the meaning consistent with the meaning in the context of prior art, and unless as here one
Sample defines, and will not explain by idealization or the most formal implication.
For ease of the understanding to the embodiment of the present invention, below in conjunction with accompanying drawing as a example by several specific embodiments
It is further explained explanation, and each embodiment is not intended that the restriction to the embodiment of the present invention.
In order to realize accurate, efficient, the low cost order-checking of DNA molecular, the one that the embodiment of the present invention provides
The structure of DNA sequencing device based on Graphene hexagonal boron nitride grapheme nano-pore as it is shown in figure 1,
Including twin polishing monocrystalline silicon piece 1, the silica (SiO being placed on twin polishing monocrystalline silicon piece 12) film
21, SiO2Film 21 grown on top has silicon nitride (Si3N4) film 20, at Si3N4It is etched with square on film 20
Shape window 7, at Si3N4Photoetching, thermal evaporation or electron beam evaporation technique is utilized to prepare chrome gold on film 20
(Cr/Au) lower layer contacts electrode 19, is coated with bottom Graphene micro-strip above lower layer contacts electrode 19
4, above bottom Graphene micro-strip 4, it is coated with hexagonal boron nitride micro-strip 18, in hexagonal boron nitride micro-strip 18
Top is coated with top layer graphene micro-strip 13, bottom Graphene micro-strip 4, hexagonal boron nitride micro-strip 18 and top layer
Graphene micro-strip 13 constitutes Graphene hexagonal boron nitride Graphene (G/h-BN/G) hetero-junctions
Structure.
Utilize photoetching and the graphical above-mentioned Graphene hexagonal boron nitride Graphene of plasma etching technology
Heterojunction structure, then utilizes photoetching, thermal evaporation or electron beam evaporation technique in top layer graphene micro-strip 13
A pair (two) top layer contact electrode 12 of side's preparation, utilizes and focuses on electron beam (FEB) or focused ion bundle
(FIB) technology is in one Asia of etching, Graphene hexagonal boron nitride Graphene hetero-junctions center suspended
The Graphene hexagonal boron nitride grapheme nano-pore 5 of 10nm.
Dual surface lithography, inductively coupled plasma (ICP) or each to different is utilized at the back side of monocrystalline silicon piece 1
Property wet etching technique make microcavity 9.Sequencing reaction chamber 2 is filled with electrolyte solution 3.Lower layer contacts electricity
Pole 19 connects positive potential, and reaction chamber is for supporting silicon nitride film and the Graphene hexagonal boron nitride on upper strata
Graphene hetero-junctions.
It is positioned at the top layer contact electrode 12 of Graphene hexagonal boron nitride grapheme nano-pore 5 arranged on left and right sides
Connect positive potential and negative potential respectively.Lower layer contacts electrode 19, top layer right contact electrode 12, longitudinal direction are the faintest
Tunnelling current measures equipment 17 and variable voltage source 16 constitutes longitudinal tunnelling current and measures loop；It is distributed in stone
A pair top layer contact electrode 12 of ink alkene hexagonal boron nitride grapheme nano-pore 5 the right and left, the most micro-
Weak tunnelling current measures equipment 14 and variable voltage source 15 constitutes horizontal tunnelling current and measures loop.It is placed in silicon
Platinum electrode 8 above sheet 1 connects positive potential, is placed in the platinum electrode 8 below silicon chip 1 and connects negative potential, platinum electrode 8,
Faint ion-conductance flow measurement device 11 and variable voltage source 10 constitute faint gas current and measure loop.
A diameter of 1 10nm of described Graphene hexagonal boron nitride grapheme nano-pore 5.
Described top layer graphene micro-strip 13 is single or multiple lift Graphene.
Described bottom Graphene micro-strip 4 is single or multiple lift Graphene.
Described hexagonal boron nitride micro-strip 18 is single or multiple lift hexagonal boron nitride.
The thickness of described silica membrane 21 is 10 50nm.
The thickness of described silicon nitride film 20 is 200 400nm.
It is pico-ampere level current measuring instrument that the faint tunnelling current of described longitudinal direction measures equipment 17.
Described longitudinal ion-conductance flow measurement device 11 is pico-ampere level current measuring instrument.
It is submicron level current measuring instrument that described horizontal faint tunnelling current measures equipment 14.
The bias voltage of described variable voltage source 10 should be 0.05 0.25V, at Graphene hexagonal boron nitride
Platinum electrode 8 above grapheme nano-pore 5 connects positive potential, at Graphene hexagonal boron nitride Graphene
Platinum electrode 8 below nano-pore 5 connects negative potential.
Described electrolyte solution 3 is NaCl, KCl or LiCl solution, and its concentration is 0.8 1.5mol/L,
PH value is 8.0.
The handling process of the preparation method of above-described DNA sequencing device is as in figure 2 it is shown, include walking as follows
Rapid:
Step 1: wash down twin polishing monocrystalline silicon piece 1.Monocrystalline silicon piece 1 is placed in the hydrogen peroxide that proportioning is 1:4
With in sulfuric acid mixture liquid, described sulfuric acid mixture liquid is heated, such as, by sulfuric acid under 85 degrees Celsius
Mixed liquor boils 15 minutes, removes the superficial stain of monocrystalline silicon piece 1, then with deionized water rinsing, drying list
Crystal silicon chip 1.
Step 2: thin by silica that hot oxide growth a layer thickness is 10 50nm on monocrystalline silicon piece 1
Film 21.
Step 3: utilize plasma enhanced chemical vapor deposition (PECVD) technology at silica membrane
21 a layer thickness grown above are the silicon nitride film 20 of 200 400nm.
Step 4: utilize photoetching and thermal evaporation or electron beam evaporation technique to prepare Graphene hexagonal boron nitride
Chrome gold lower layer contacts electrode 19 bottom Graphene hetero-junctions.First at silicon nitride film 4 front spin coating light
Photoresist, is engraved in electrode zone by light and forms photoresist perforate, then use thermal evaporation or electron beam evaporation
Deposition techniques chrome gold, finally uses stripping lift-off to complete the preparation of lower layer contacts electrode 19.
Step 5: utilize dual surface lithography technology and inductively coupled plasma (ICP) or anisotropic wet
Lithographic technique goes out microcavity 9 at monocrystalline silicon piece 1 back-etching, with silica membrane 21 for etching self-stopping technology
Layer, microcavity 9 top dimension is 5-20 μm, and microcavity 9 bottom size is by the lithographic technique used and silicon substrate
Thickness determines.
Step 6: utilize photoetching technique and reactive ion etching technology (RIE) to make on silicon nitride film 20
Making a rectangular window 7, the size of rectangular window 7 is 0.5 3 μm, for the Graphene of support suspension
Hexagonal boron nitride Graphene heterojunction structure.
Step 7: utilize polymethyl methacrylate (PMMA) transfer bottom Graphene micro-strip 4 to bottom to connect
In touched electrode 19 and silicon nitride film 20, as the tunnel of Graphene hexagonal boron nitride Graphene hetero-junctions
Wear electrode.
Step 8: utilize polymethyl methacrylate (PMMA) to shift hexagonal boron nitride micro-strip 18 to bottom stone
In ink alkene micro-strip 4, as the dielectric layer of Graphene hexagonal boron nitride Graphene hetero-junctions.
Step 9: utilize polymethyl methacrylate (PMMA) to shift top layer graphene micro-strip 13 to six side's nitrogen
Change in boron micro-strip 18, as electrode in the tunnelling of Graphene hexagonal boron nitride Graphene hetero-junctions, and
Utilize photoetching and plasma etching technology patterned graphene hexagonal boron nitride Graphene hetero-junctions
Structure.
Step 10: utilize photoetching and thermal evaporation or electron beam evaporation technique to make in top layer graphene micro-strip 13
Standby a pair (two) chrome gold top layer contact electrode 12.
Step 11: utilize and focus on electron beam (FEB) or focused ion bundle (FIB) technology at the stone suspended
The Graphene six side nitridation of ink alkene hexagonal boron nitride Graphene hetero-junctions center one sub-10nm of etching
Boron grapheme nano-pore 5, nano-pore 5 contacts the centre of electrode 12 at two top layers.
Step 12: will be installed on the sequence testing chip of Graphene hexagonal boron nitride grapheme nano-pore 5
In sequencing reaction chamber 2；Contact at lower layer contacts electrode 19 and right side top layer and between electrode 12, access variable voltage
Source 16 and longitudinally faint tunnelling current measure equipment 17；It is being positioned at Graphene hexagonal boron nitride Graphene
Variable voltage source 15 and horizontal faint tunnelling is accessed between the top layer contact electrode 12 of nano-pore 5 arranged on left and right sides
Current measure device 14；Access between two platinum electrodes 8 and drive single strand dna 7 to pass through Graphene six
The variable voltage source 10 of side's boron nitride grapheme nano-pore 5 and faint ion-conductance flow measurement device 11,
Obtain DNA sequencing device based on Graphene hexagonal boron nitride grapheme nano-pore.
In sum, the embodiment of the present invention proposes based on Graphene hexagonal boron nitride Graphene solid-state
The Novel DNA sequencing device of nano-pore, utilizes traditional silicon materials and novel two-dimensional material Graphene and six
A kind of novel graphite alkene hexagonal boron nitride Graphene solid nano pore structure of side's boron nitride design, and
Prior art is compared and is had the advantage that
1), the employing of Graphene hexagonal boron nitride grapheme nano-pore, solve conventional solid nanometer
The oversize problem causing order-checking resolution ratio to be difficult to reach single base of hole path.Additionally, hexagonal boron nitride is excellent
Different dielectric characteristic so that the top layer graphene in Graphene hexagonal boron nitride Graphene hetero-junctions
Micro-strip and bottom Graphene micro-strip can be natural sub-nanometer scale (hexagonal boron nitride thickness) as a pair
Accurately alignment and the tunnelling electrode of good isolation, overcome tunnelling electrode in tunnelling current DNA sequencing method and be difficult to
The problem made.These advantages are laid a good foundation for the single base discrimination rate of realization, the order-checking of direct nano-pore.
2) use Graphene hexagonal boron nitride grapheme nano-pore as DNA sequencing due to the present invention
Core component, when DNA molecular passes through nano-pore, can be simultaneously to ion-conductance flow resistance longitudinal in nano-pore
Laterally tunnelling current change, nano-pore top layer and bottom Graphene in plug, nano-pore top layer graphene micro-strip
Between micro-strip, longitudinal tunnelling current change measures, and comes accurate eventually through three groups of data carry out analytical Calculation
Really obtain DNA molecular sequence information.The present invention is expected to improve Conventional nano ionic porogen current blockade DNA and surveys
Sequence method signal to noise ratio is low, easy by problems such as external environmental interference, improves order-checking precision, fundamentally solves to receive
Metre hole DNA sequencing problem encountered.
One of ordinary skill in the art will appreciate that: accompanying drawing is the schematic diagram of an embodiment, in accompanying drawing
Module or flow process not necessarily implement necessary to the present invention.
Each embodiment in this specification all uses the mode gone forward one by one to describe, identical between each embodiment
Similar part sees mutually, and what each embodiment stressed is different from other embodiments
Part.For device or system embodiment, owing to it is substantially similar to embodiment of the method,
So describing fairly simple, relevant part sees the part of embodiment of the method and illustrates.Above retouched
The Apparatus and system embodiment stated is only schematically, the wherein said unit illustrated as separating component
Can be or may not be physically separate, the parts shown as unit can be or also may be used
Not to be physical location, i.e. may be located at a place, or multiple NE can also be distributed to
On.Some or all of module therein can be selected according to the actual needs to realize the present embodiment scheme
Purpose.Those of ordinary skill in the art, in the case of not paying creative work, are i.e. appreciated that also
Implement.
The above, the only present invention preferably detailed description of the invention, but protection scope of the present invention is not
Being confined to this, any those familiar with the art, can in the technical scope that the invention discloses
The change readily occurred in or replacement, all should contain within protection scope of the present invention.Therefore, the present invention
Protection domain should be as the criterion with scope of the claims.
Claims (10)
1. a DNA sequencing device, it is characterised in that including:
The lower layer contacts electrode being arranged on twin polishing monocrystalline silicon piece, covers above lower layer contacts electrode
There is bottom Graphene micro-strip, above bottom Graphene micro-strip, be coated with hexagonal boron nitride micro-strip, six sides
Top layer graphene micro-strip, bottom Graphene micro-strip, hexagonal boron nitride micro-strip it is coated with above boron nitride micro-strip
A Graphene hexagonal boron nitride Graphene heterojunction structure is constituted, at stone with top layer graphene micro-strip
Ink alkene hexagonal boron nitride Graphene hetero-junctions center etching Graphene hexagonal boron nitride Graphene is received
Metre hole.
DNA sequencing device the most according to claim 1, it is characterised in that include being placed in twin polishing
Silica membrane on monocrystalline silicon piece, this silica membrane grown on top has silicon nitride film, at nitrogen
It is etched with rectangular window on SiClx film, silicon nitride film utilizes photoetching and thermal evaporation or electron beam steam
The technology of sending out prepares chrome gold lower layer contacts electrode.
DNA sequencing device the most according to claim 2, it is characterised in that utilize photoetching and plasma
Body lithographic technique patterned graphene hexagonal boron nitride Graphene heterojunction structure, utilizes photoetching and heat to steam
Send out or electron beam evaporation technique prepares two top layer contact electrodes above top layer graphene micro-strip, utilize poly-
Burnt electron beam or focused ion beam technology are in the Graphene hexagonal boron nitride Graphene hetero-junctions suspended
The Graphene hexagonal boron nitride grapheme nano-pore of the heart one sub-10nm of etching.
DNA sequencing device the most according to claim 3, it is characterised in that at the back side of monocrystalline silicon piece
Utilize dual surface lithography, inductively coupled plasma or anisotropic wet etch fabrication techniques microcavity, order-checking
Being filled with electrolyte solution in reaction chamber, reaction chamber is for supporting silicon nitride film and the Graphene on upper strata
Hexagonal boron nitride Graphene hetero-junctions.
Lower layer contacts electrode connects positive potential, be positioned at Graphene hexagonal boron nitride grapheme nano-pore left,
The top layer contact electrode of right both sides connects positive potential and negative potential respectively.
DNA sequencing device the most according to claim 4, it is characterised in that lower layer contacts electrode, top
Layer right contact electrode, longitudinally faint tunnelling current measure equipment and variable voltage source constitutes longitudinal tunnelling electricity
Flow measurement loop；
It is distributed in a pair top layer contact electricity of Graphene hexagonal boron nitride grapheme nano-pore the right and left
Equipment is measured in pole, horizontal faint tunnelling current and variable voltage source constitutes horizontal tunnelling current and measures loop；
It is placed in the platinum electrode above monocrystalline silicon piece and connects positive potential, be placed in the platinum electrode below monocrystalline silicon piece and connect negative
Current potential, platinum electrode, faint ion-conductance flow measurement device and variable voltage source constitute faint gas current and measure
Loop.
DNA sequencing device the most according to claim 3, it is characterised in that: described Graphene six side
A diameter of 1 10nm of boron nitride grapheme nano-pore.
DNA sequencing device the most according to claim 1, it is characterised in that: described top layer graphene is micro-
Band is single or multiple lift Graphene, and described bottom Graphene micro-strip is single or multiple lift Graphene, described six
Side's boron nitride micro-strip is single or multiple lift hexagonal boron nitride.
DNA sequencing device the most according to claim 3, it is characterised in that: it is used for driving single stranded DNA
Molecule is provided through the electrostatic field of Graphene hexagonal boron nitride grapheme nano-pore by variable voltage source,
The bias voltage of described variable voltage source should be 0.05 0.25V, at Graphene hexagonal boron nitride graphite
Platinum electrode above alkene nano-pore connects positive potential, under Graphene hexagonal boron nitride grapheme nano-pore
The platinum electrode of side connects negative potential.
DNA sequencing device the most according to claim 1, it is characterised in that: at Graphene six side's nitrogen
Change the right contact one on negative potential in boron grapheme nano-pore top layer graphene, at bottom Graphene
On lower layer contacts electrode connect positive potential, about Graphene hexagonal boron nitride grapheme nano-pore two
A pair top layer contact electrode on limit connects positive potential and negative potential respectively.
10. the preparation method of a DNA sequencing device, it is characterised in that comprise the steps:
Step 1: wash down twin polishing monocrystalline silicon piece, monocrystalline silicon piece is placed in hydrogen peroxide that proportioning is 1:4 and
In sulfuric acid mixture liquid, described sulfuric acid mixture liquid is heated, remove the superficial stain of monocrystalline silicon piece, so
Afterwards with deionized water rinsing, dry monocrystalline silicon piece；
Step 2: by hot oxide growth layer of silicon dioxide film on monocrystalline silicon piece；
Step 3: utilize plasma enhanced chemical vapor deposition technology at silica membrane grown above
Layer silicon nitride film；
Step 4: utilize photoetching and thermal evaporation or electron beam evaporation technique to prepare Graphene hexagonal boron nitride
Chrome gold lower layer contacts electrode bottom Graphene hetero-junctions；
Step 5: utilize dual surface lithography technology and inductively coupled plasma or anisotropic wet etch technology
Microcavity is gone out at monocrystalline silicon piece back-etching；
Step 6: utilize photoetching technique and reactive ion etching technology to make a rectangle on silicon nitride film
Window, this rectangular window is for the Graphene hexagonal boron nitride Graphene heterojunction structure of support suspension；
Step 7: utilize polymethyl methacrylate transfer bottom Graphene micro-strip to lower layer contacts electrode and nitrogen
On SiClx film, as the tunnelling bottom electrode of Graphene hexagonal boron nitride Graphene hetero-junctions；
Step 8: utilize polymethyl methacrylate transfer hexagonal boron nitride micro-strip to bottom Graphene micro-strip
On, as the dielectric layer of Graphene hexagonal boron nitride Graphene hetero-junctions；
Step 9: utilize polymethyl methacrylate transfer top layer graphene micro-strip to hexagonal boron nitride micro-strip
On, as electrode in the tunnelling of Graphene hexagonal boron nitride Graphene hetero-junctions, and utilize photoetching and
Plasma etching technology patterned graphene hexagonal boron nitride Graphene heterojunction structure；
Step 10: utilize photoetching and thermal evaporation or electron beam evaporation technique to prepare in top layer graphene micro-strip
Two chrome gold top layer contact electrodes；
Step 11: utilize and focus on electron beam or focused ion beam technology in the Graphene six side nitridation suspended
The Graphene hexagonal boron nitride graphene nano of boron Graphene hetero-junctions center one sub-10nm of etching
Hole, this Graphene hexagonal boron nitride grapheme nano-pore contacts the centre of electrode at two top layers；
Step 12: will be installed on the sequence testing chip of Graphene hexagonal boron nitride grapheme nano-pore
In sequencing reaction chamber；Lower layer contacts electrode and right side top layer contact access between electrode variable voltage source and
Longitudinally faint tunnelling current measures equipment；It is being positioned at Graphene hexagonal boron nitride grapheme nano-pore
Access variable voltage source between the top layer contact electrode of arranged on left and right sides and horizontal faint tunnelling current measurement sets
Standby；Access between two platinum electrodes and drive single strand dna to pass through Graphene hexagonal boron nitride graphite
The variable voltage source of alkene nano-pore and faint ion-conductance flow measurement device.
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| CN107265396A (en) * | 2017-05-13 | 2017-10-20 | 南开大学 | The single-layer graphene unimolecule knot preparation method of Mechanical controllable nano gap |
| WO2019000158A1 (en) * | 2017-06-26 | 2019-01-03 | 武汉科技大学 | Tunnel identification technology-based nano detection device and method |
| CN109459373A (en) * | 2018-11-08 | 2019-03-12 | 海南大学 | A kind of super-elasticity particle modulus of shearing detection device and method based on nano-pore |
| CN109775659A (en) * | 2019-01-28 | 2019-05-21 | 中国科学院微电子研究所 | Nano-pore structure, the device and method for controlling nano-pore size |
| CN110272018A (en) * | 2019-05-15 | 2019-09-24 | 广东工业大学 | A kind of manufacturing method in double-layer nanometer hole |
| CN112300913A (en) * | 2020-11-11 | 2021-02-02 | 深圳市儒翰基因科技有限公司 | DNA sequencing device, solid-state nanopore array and preparation method thereof |
| CN113406162A (en) * | 2021-06-03 | 2021-09-17 | 浙江大学 | Preparation method for forming nano-gap electrode pair |
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